Hanmi, Yuhan and HK inno.N are pursuing new mechanisms to address muscle loss, rebound weight gain and adherence issues.
Global big pharma is already betting on the next wave, but latecomers must prove both weight loss and safety.
An obesity drug-related image generated by Google’s AI Gemini.
[Insight Korea = An Hye-wan]
Over the past two years, the global obesity drug market has been driven above all by Wegovy and Mounjaro. But GLP-1 obesity drugs still have side effects and limitations, including muscle loss, weight regain and low medication adherence.
As a result, pharmaceutical and biotech companies in Korea and abroad are accelerating the development of next-generation obesity drugs. Among Korean companies, Hanmi Pharmaceutical, HK inno.N and Yuhan are moving into “non-incretin” obesity drugs that reduce weight through mechanisms different from GLP-1.
Incretins are a group of hormones secreted by the small intestine when food enters the body. They promote insulin secretion from the pancreas, with GLP-1 and GIP being the best-known examples. Wegovy, or semaglutide, and Mounjaro, or tirzepatide, both stimulate GLP-1 receptors to reduce appetite and slow gastric emptying, producing weight loss of 15 to 20 percent. Non-incretin obesity drugs do not act on these receptors. Instead, they reduce fat through other pathways such as amylin, CRF2 and CB1.
Hanmi, Yuhan and HK inno.N Enter Non-Incretin Development
Among Korean companies, Hanmi Pharmaceutical has advanced the fastest into the clinical stage. On Nov. 6 last year, Hanmi received approval from the U.S. Food and Drug Administration for its investigational new drug application for a Phase 1 trial of HM17321, a non-incretin obesity candidate.
HM17321 is a peptide candidate that acts on the CRF2 receptor. Without stimulating incretin receptors, it aims for “quality weight loss” by increasing muscle while reducing fat. According to the company, these effects were confirmed in preclinical studies, and Hanmi is developing the drug with a target of commercialization in 2031.
“HM17321 is not simply a drug that reduces weight. It is fundamentally differentiated from existing treatments because it simultaneously pursues integrated benefits, including fat reduction, muscle increase, and improvement in exercise and metabolic function,” said Choi In-young, head of Hanmi Pharmaceutical’s R&D center. “Hanmi views obesity as a root cause of metabolic disease.”
Yuhan is also accelerating non-incretin development. Its non-incretin candidates, YH-Obesity-1 and YH-Obesity-2, are oral candidates with mechanisms differentiated from GLP-1. Their target is one of several pathways including amylin, CRF2 and CB1. Yuhan has not disclosed the specific target, and the program remains in the discovery stage. In addition to YH-Obesity, all GLP-1 candidates under development by Yuhan are also being developed as oral drugs.
HK inno.N is the latest mover among the three. On April 27, the company signed a joint research and development agreement for next-generation obesity treatments with Atomatrix, an AI-based drug design company. Through Atomatrix’s molecular dynamics-based drug design platform CANDDIE, HK inno.N is seeking to discover non-incretin small-molecule candidates.
“We are pursuing non-incretin new drugs that can overcome the gastrointestinal side effects and muscle loss limitations of existing obesity treatments,” said Park Byung-chul, head of HK inno.N’s drug research institute. The target class and timing for clinical entry have not been disclosed.
Big Pharma Bets on the Post-GLP-1 Market
Global big pharma is already moving ahead. Roche, AbbVie, Pfizer, Eli Lilly and Novo Nordisk have since last year been acquiring companies with non-incretin candidates or directly developing such drugs themselves.
The most advanced example is Novo Nordisk. The company has completed Phase 3 trials of CagriSema, an amylin and GLP-1 combination therapy, and applied for approval from the U.S. FDA in December last year.
The reason pharmaceutical and biotech companies at home and abroad are actively pursuing non-incretin obesity drugs begins with the side effects of GLP-1. GLP-1 drugs have long faced concerns over muscle loss. In the STEP 1 trial, a pivotal trial for Wegovy, research showed that about 40 percent of the weight lost was lean mass, including muscle. Other studies have also found that 20 to 40 percent of lost weight can be muscle.
In addition, studies suggesting cardiovascular risks after discontinuation have raised concerns that these drugs may need to be taken for life. This is why the industry has turned its attention to non-incretin targets such as amylin, a pancreatic hormone; CRF2, linked to stress hormone signaling; and CB1, part of the endocannabinoid system.
Experts say that for latecomer non-incretin obesity drugs to succeed, they must not only differentiate themselves from GLP-1 but also prove weight-loss efficacy and safety.
“GLP-1 is already an established market, and the leading companies are highly competitive,” said Lee Seung-kyu, vice chairman of the Korea Biotechnology Industry Organization. “Latecomers are trying to enter the market by using new modalities, changing formulations from injections to oral drugs, or reducing side effects.”
“The biggest strength and weakness of latecomers ultimately comes down to weight-loss numbers,” Lee said. “They need to show numbers similar to or better than the weight-loss standards set by Wegovy and Mounjaro, and whatever the approach, they must reach those numbers while also securing safety.”
- This article was translated by ChatGPT. (이 기사는 챗GPT가 번역했습니다.)
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